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beta 2-syntrophin and Par-3 promote an apicobasal Rac activity gradient at cell-cell junctions by differentially regulating Tiam1 activity

Mack, Natalie A.; Porter, Andrew P.; Whalley, Helen J.; Schwarz, Juliane P.; Jones, Richard C.; Syed Khaja, Azharuddin Sajid LU ; Bjartell, Anders LU ; Anderson, Kurt I. and Malliri, Angeliki (2012) In Nature Cell Biology 14(11). p.1169-1180
Abstract
Although Rac and its activator Tiam1 are known to stimulate cell-cell adhesion, the mechanisms regulating their activity in cell-cell junction formation are poorly understood. Here, we identify beta 2-syntrophin as a Tiam1 interactor required for optimal cell-cell adhesion. We show that during tight-junction (TJ) assembly beta 2-syntrophin promotes Tiam1-Rac activity, in contrast to the function of the apical determinant Par-3 whose inhibition of Tiam1-Rac activity is necessary for TJ assembly. We further demonstrate that beta 2-syntrophin localizes more basally than Par-3 at cell-cell junctions, thus generating an apicobasal Rac activity gradient at developing cell-cell junctions. Targeting active Rac to TJs shows that this gradient is... (More)
Although Rac and its activator Tiam1 are known to stimulate cell-cell adhesion, the mechanisms regulating their activity in cell-cell junction formation are poorly understood. Here, we identify beta 2-syntrophin as a Tiam1 interactor required for optimal cell-cell adhesion. We show that during tight-junction (TJ) assembly beta 2-syntrophin promotes Tiam1-Rac activity, in contrast to the function of the apical determinant Par-3 whose inhibition of Tiam1-Rac activity is necessary for TJ assembly. We further demonstrate that beta 2-syntrophin localizes more basally than Par-3 at cell-cell junctions, thus generating an apicobasal Rac activity gradient at developing cell-cell junctions. Targeting active Rac to TJs shows that this gradient is required for optimal TJ assembly and apical lumen formation. Consistently, beta 2-syntrophin depletion perturbs Tiam1 and Rac localization at cell-cell junctions and causes defects in apical lumen formation. We conclude that beta 2-syntrophin and Par-3 fine-tune Rac activity along cell-cell junctions controlling TJ assembly and the establishment of apicobasal polariy. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Cell Biology
volume
14
issue
11
pages
1169 - 1180
publisher
Nature Publishing Group
external identifiers
  • wos:000310778100010
  • scopus:84869085252
ISSN
1465-7392
DOI
10.1038/ncb2608
language
English
LU publication?
yes
id
16889f79-3dad-4007-bb8c-9500896edef0 (old id 3259641)
date added to LUP
2013-01-07 09:39:15
date last changed
2017-11-19 03:55:32
@article{16889f79-3dad-4007-bb8c-9500896edef0,
  abstract     = {Although Rac and its activator Tiam1 are known to stimulate cell-cell adhesion, the mechanisms regulating their activity in cell-cell junction formation are poorly understood. Here, we identify beta 2-syntrophin as a Tiam1 interactor required for optimal cell-cell adhesion. We show that during tight-junction (TJ) assembly beta 2-syntrophin promotes Tiam1-Rac activity, in contrast to the function of the apical determinant Par-3 whose inhibition of Tiam1-Rac activity is necessary for TJ assembly. We further demonstrate that beta 2-syntrophin localizes more basally than Par-3 at cell-cell junctions, thus generating an apicobasal Rac activity gradient at developing cell-cell junctions. Targeting active Rac to TJs shows that this gradient is required for optimal TJ assembly and apical lumen formation. Consistently, beta 2-syntrophin depletion perturbs Tiam1 and Rac localization at cell-cell junctions and causes defects in apical lumen formation. We conclude that beta 2-syntrophin and Par-3 fine-tune Rac activity along cell-cell junctions controlling TJ assembly and the establishment of apicobasal polariy.},
  author       = {Mack, Natalie A. and Porter, Andrew P. and Whalley, Helen J. and Schwarz, Juliane P. and Jones, Richard C. and Syed Khaja, Azharuddin Sajid and Bjartell, Anders and Anderson, Kurt I. and Malliri, Angeliki},
  issn         = {1465-7392},
  language     = {eng},
  number       = {11},
  pages        = {1169--1180},
  publisher    = {Nature Publishing Group},
  series       = {Nature Cell Biology},
  title        = {beta 2-syntrophin and Par-3 promote an apicobasal Rac activity gradient at cell-cell junctions by differentially regulating Tiam1 activity},
  url          = {http://dx.doi.org/10.1038/ncb2608},
  volume       = {14},
  year         = {2012},
}